Overview

Systematic Review Conclusion

Flurbiprofen 50 mg or 100 mg is an effective analgesic in postoperative pain. The NNT for at least 50% pain relief is 2.5 and similar to that of other common NSAIDs, with a 6-hour duration.

Critical Summary Assessment

This systematic review of 11 trials of acceptable quality, but had a limited number of participants (1,646 total, 362 placebo). The review suggests that single doses of flurbiprofen 25 mg to 100 mg provide relief of moderate to severe postoperative pain in 35 to 65 percent of adult subjects across 4 to 6 hours, with a substantial number of studies with dental pain following extraction. Higher doses appear to provide better pain relief without a corresponding increase in adverse effects that were similar to placebo.

Evidence Quality Rating

Limited Evidence

Structured Abstract

Clinical Questions:

What is the efficacy and safety of a single oral dose of flurbiprofen compared to placebo in adults with moderate to severe postoperative pain?

Review Methods:

The authors used four electronic databases to review all studies to January, 2009. They adhered to a protocol. Two independent authors assessed trial quality and extracted data. They extracted pain relief or pain intensity data to determine the number of participants who experienced 50% or more pain relief within a 4- to 6-hour period after receiving a single oral dose of flurbiprofen as compared to placebo. The authors calculated as measures of efficacy number needed to treat (NNT) and relative risk (RR). They evaluated adverse events, the need for rescue medication and participant withdrawals as secondary outcome measures.

Main Results:

A review of 11 RCTs evaluated the analgesic effect of doses of flurbiprofen from 25 mg to 150 mg, with most information reported for 50 mg and 100 mg. 8 studies involved a tooth-extraction pain model. For at least 50% pain relief compared with placebo the NNT for flurbiprofen 50 mg was 2.7 (2.3-3.3) and for flurbiprofen 100 mg was 2.8 (2.2-3.6). The proportion with at least 50% pain relief was 69% with 50 mg and 65% with 200 mg. The proportion of subjects requiring rescue medication was 25 percent for the 50-mg dose and 16 percent for 100 mg. Adverse events did not differ from those seen with placebo. Withdrawals were attributed to protocol violations.

Conclusion:

Flurbiprofen at doses of 50 and 100 mg provides effective analgesia in 65 to 70 percent of adults with moderate or severe postoperative pain, compared with 25 to 30 percent with placebo. The NNT of 2.5 for at least 50 percent pain relief over four to six hours compares with that of standard doses of other commonly used NSAIDs, such as ibuprofen 400 mg. The NNT for rescue medication with six hours, at 2.0, is lower than that of ibuprofen, implying a longer duration of action.

Source of Funding:

Commentary

Importance and Context:

Nonsteroidal anti-inflammatory drugs (NSAIDS) are first-choice agents for the management of both pre- and postoperative pain in dentistry, particularly since unlike opioids, they do not impair consciousness. Based on limited current evidence, 50- and 100-mg doses of flurbiprofen may offer the short-term management of moderate to severe postoperative pain in adults.

Strengths and Weaknesses of the Systematic Review:

This high-quality systematic review included a comprehensive search, using defined inclusion and exclusion criteria, and no language restrictions. The auhtors did not search abstracts, conference proceedings and other grey literature. They did not contact the manufacturing pharmaceutical companies were not contacted for unpublished trial data. Two authors independently assessed trial quality and extracted data, and resolved disagreements through consensus or by third author. Standard guidelines for data analysis and heterogeneity were performed. The authors did not evaluate flurbiprofen treatment parameters, such as dose per subject weight or timing of dose related to the procedure. They also did not evaluate multiple dose administrations. The authors disclosed they received fees from pharmaceutical companies for lectures related to analgesics and other healthcare interventions.

Strengths and Weaknesses of the Evidence:

Included studies were randomized and double-blinded to minimize bias, although other reviews of single-dose, postoperative analgesics have included far greater numbers of studies and participants. The majority of studies evaluated single flurbiprofen doses of 50 and 100 mg. Reporting of data for adverse events and participant withdrawals was not always complete. Long-term, multiple-dose studies should be used for assessing the incidence of adverse effects, as multiple doses are frequently needed in short-term pain management.

Implications for Dental Practice:

There is limited, high-quality evidence that flurbiprofen in doses of 50 mg and 100 mg effectively and safely drug for the management of postoperative pain in adults over a longer period of time than other commonly prescribed NSAIDs. The dose of flurbiprofen administered should be based on the practitioner’s experience, severity of dental pain, patient’s weight and sensitivity to adverse effects. Flurbiprofen is not recommended for patients who are allergic to NSAIDs or aspirin, pregnant, or who are at risk of complications of thromboembolism (1). Currently, the evidence of high-quality systematic reviews favors the use of traditional, non-selective NSAIDs like flurbiprofen as the first choice of drug for managing moderate to severe postoperative pain, although it lacks some of the advantages of ibuprofen, including availability over the counter.
REFERENCES
1. Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of Nonsteroidal Antiinflammatory Drugs, An Update for Clinicians: A Scientific Statement From the American Heart Association. Circulation. 2007;115:1634-1642.